EP3697727B1 - Method for manufacturing a microstructured device - Google Patents

Description

The invention relates to the field of microstructured devices.

More specifically, the invention proposes a method for manufacturing a microstructured device, in particular a microfluidic device.

There are different techniques for fabricating microstructured devices.

Among these techniques, mention may be made of microfabrication, which notably covers micromachining or photolithography. Micromachining consists of directly machining a microstructure (for example a channel for microfluidic applications, or a cavity for other applications) in a plastic material. The plastic material is then bonded to a substrate to form the channels. Photolithography uses the classic techniques of microelectronics. For example, one can refer to C. Iliescu, Microfluidics in Glass: Technologies and Applications. Informacije MIDEM 36(2006), vol. 4 or at Y. Xia & al., Soft lithography, Angew. Chem. Int. Ed. 1998, vol. 37, p. 550-575 , depending on the nature of the substrate.

More recently, it has been proposed to rely on the possibilities offered by printing, in particular inkjet printing. For example, we can refer to N. Bhattacharjee & al., Lab Chip, 2016, vol. 16, p. 1720-1742 to identify the various sub-techniques that may be classified under printing technique.

Among these sub-techniques falling within the scope of printing, inkjet printing, or what amounts to substantially the same thing, printing via a syringe comprising the ink, is widely used. . Here, the idea is to deposit on a substrate an ink intended to solidify and to form a negative pattern of a microstructure (for example a channel for microfluidic applications) of the device being manufactured. The pattern and the substrate are then covered by an envelope. Then, the or each negative pattern is eliminated. There then remains the envelope on the substrate, the microstructure then being formed in the envelope.

Here, the critical step lies in the elimination of the pattern, necessary to achieve the microstructure.

A classic approach to removing the pattern is to apply a jet of fluid (especially water) under high pressure. The problem with this approach is that it involves mechanical stresses on the substrate and on the envelope, and in particular at the level of the interface between the envelope and the substrate. It is therefore possible to unseal the microstructured device and, if this is not the case, to deform it.

Moreover, this approach can only work for microfluidic applications (presence of a channel and consequently of openings allowing the evacuation of the pattern by the jet of fluid. In other words, this approach is not applicable when the pattern serves to form a cavity, as may be the case for other applications (optics, for example).

Another approach is to use a particular pattern.

Thus, the article of Thierrault et al, “Chaotic mixing in three-dimensional microvascular networks fabricated by direct-write assembly”, Nature materials, vol. 2, April 2003, p. 265-347 , proposes the use of an organic ink of the paraffin type, which is in the form of a paste at room temperature. This paste is then liquefied (by heating) and sucked out.

With this other approach, the risk of unsealing or deforming the microstructured device is reduced.

However, this other approach remains limited to a particular type of ink. This therefore limits the types of devices that can be obtained.

Moreover, this other approach also remains limited to microfluidic applications, insofar as it remains necessary to have openings to evacuate the pattern once liquefied.

US2014/183044 And US 2005/151285 disclose methods of fabricating a microstructured device on a substrate using a solidified ink layer as the sacrificial material which is used to form the particular shape of a polymeric structure deposited on the ink layer.

Thus, an object of the invention is to propose an improved method of manufacturing a microstructured device.

In particular, one objective of the invention is to be able to broaden the range of materials which can be envisaged for producing the device.

Also in particular, another objective of the invention is to be able to have access to fields other than microfluidics, in which the pattern aims to form a cavity. In this case, it is indeed important to be able to evacuate the pattern without the presence of openings allowing this evacuation.

1. a) fournir un substrat ;
2. b) imprimer une encre, non solide, sur le substrat, l'encre se solidifiant au contact du substrat pour former un motif en négatif d'au moins une microstructure du dispositif microstructuré à fabriquer ;
3. c) envelopper l'encre sous forme solide avec un polymère non réticulé et comportant un additif apte à permettre une réticulation dudit polymère, ledit polymère étant non miscible avec le motif obtenu à l'étape b) afin de former une enveloppe pour le motif, ledit polymère présentant une température de fusion strictement supérieure à la température de sublimation ou d'évaporation de l'encre formant le motif ;
4. d) réticuler l'enveloppe ; puis
5. e) sublimer ou, selon la nature de l'encre, liquéfier puis évaporer l'encre de sorte à former le dispositif microstructuré comportant ladite au moins une microstructure.

To this end, the invention proposes a method for manufacturing a microstructured device comprising the following steps:

1. a) providing a substrate;
2. b) printing a non-solid ink on the substrate, the ink solidifying on contact with the substrate to form a negative pattern of at least one microstructure of the microstructured device to be manufactured;
3. c) enveloping the ink in solid form with a non-crosslinked polymer and comprising an additive capable of allowing crosslinking of said polymer, said polymer being immiscible with the pattern obtained in step b) in order to form an envelope for the pattern, said polymer having a melting temperature strictly higher than the sublimation or evaporation temperature of the ink forming the pattern;
4. d) cross-linking the envelope; Then
5. e) sublimating or, depending on the nature of the ink, liquefying then evaporating the ink so as to form the microstructured device comprising said at least one microstructure.

• le substrat fourni à l'étape a) est un matériau hydrophobe choisi parmi : les polyimides (PI), les silicones dont le polydiméthylsiloxane (PDMS), le poplypropylène (PP), le polytétrafluoroéthylène (PTFE), le copolymère d'oléfine cyclique (COC) ou un matériau hydrophile choisi parmi le silicium, le verre, la cellulose, les fibres de verre ;
• entre l'étape a) et l'étape b), on réalise un traitement du substrat pour améliorer sa force d'adhésion avec l'encre à déposer et/ou le polymère destiné à former l'enveloppe ;
• au moins au cours de l'étape b), le substrat est refroidi à une température inférieure à la température de solidification de l'encre ;
• l'étape b) s'effectue sous une atmosphère présentant une humidité relative ne dépassant pas 30%, voire 15% ;
• au cours de l'étape b), l'impression s'effectue de sorte que chaque extrémité du motif en négatif de ladite au moins une microstructure du dispositif microstructuré à fabriquer se situe en bordure du substrat, de sorte que chaque extrémité puisse, sur le dispositif à fabriquer, former une ouverture, telle qu'une entrée ou une sortie de fluide, de sorte à former une microstructure se présentant sous la forme d'un canal ;
• entre l'étape b) et l'étape c), on réalise les sous-étapes suivantes : placer une connexion microfluidique, en partie au niveau de la région du motif qui est destinée à former une ouverture de canal et en partie à l'extérieur du substrat ; et appliquer de l'encre entre ladite connexion et le motif ;
• entre les étapes b) et c), on réalise un recuit, à une température avantageusement comprise entre 10% et 80% de la température de fusion du motif ;
• l'étape c) est réalisée en coulant le polymère sur le substrat imprimé par le motif ;
• le polymère introduit à l'étape c) est choisi parmi : le polydiméthylsiloxane (PDMS), les polyimides, les gels d'agarose ou une colle telle que l'acrylique ;
• l'additif présent dans le polymère est choisi parmi un agent réticulant, un photo-initiateur ou un solvant ;
• ledit polymère destiné à former l'enveloppe présente une température de fusion strictement supérieure à 110% de la température de sublimation ou d'évaporation de l'encre formant le motif ;
• l'étape e) s'effectue par chauffage et en appliquant un différentiel de pression entre l'intérieur de l'ensemble formé à l'issue de l'étape d) et l'extérieur ;
• la liquéfaction puis l'évaporation de l'encre à l'étape e) est réalisée par chauffage ;
• l'encre est choisie parmi :
  • les glycols linéaires dont la formule brute générique est C_2nH_4n+2O₂ où n est un nombre entier positif supérieur ou égal à 1, de préférence tel que n = 3, 4 ou 5 ;
  • le cyclohexanediol ;
  • le biphényl ;
  • le tri(cyclohexyl)méthane ;
  • les alcools de formule brute C_nH_2n+₂O où n est un nombre entier positif supérieur ou égal à 1, de préférence tel que n = 10, 11 ou 12 ;
• au cours de l'étape b) on imprime plusieurs couches d'encre successives les unes sur les autres ;
• l'étape b) s'effectue par impression par jet d'encre, au moyen d'une buse d'impression et d'une encre liquide dont la viscosité est inférieure ou égale à 30 mPa.s^-1 ;
• la distance entre d'une part, ladite buse d'impression et d'autre part, le substrat est comprise entre 0,5mm et 20mm ; la taille d'une goutte d'encre éjectée par ladite buse d'impression est comprise entre 10µm et 100µm; la fréquence d'éjection des gouttes d'encre de ladite buse est comprise entre 50Hz et 5kHz ; le substrat d'une déplacement relatif de l'un par rapport à l'autre avec une vitesse de déplacement relative contrôlée, comprise entre 1mm/s et 100mm/s ;
• l'étape b) s'effectue au moyen d'une seringue contenant l'encre ;
• la distance entre d'une part, une extrémité de la seringue par laquelle l'encre est dispensée et d'autre part, le substrat est comprise entre 0,1mm et 1mm ; le débit d'encre dispensé par l'extrémité de ladite seringue est compris entre 0,01 nl/s et 10 nl/s ; le substrat d'une part et, ladite extrémité de seringue d'autre part, étant adaptés pour autoriser un déplacement relatif de l'un par rapport à l'autre avec une vitesse de déplacement relative contrôlée, comprise entre 0,1mm/s et 10mm/s.

The method according to the invention may also comprise at least one of the following characteristics, taken alone or in combination:

• the substrate provided in step a) is a hydrophobic material chosen from: polyimides (PI), silicones including polydimethylsiloxane (PDMS), polypropylene (PP), polytetrafluoroethylene (PTFE), cyclic olefin copolymer ( COC) or a hydrophilic material chosen from silicon, glass, cellulose, glass fibers;
• between step a) and step b), the substrate is treated to improve its adhesion strength with the ink to be deposited and/or the polymer intended to form the envelope;
• at least during step b), the substrate is cooled to a temperature below the solidification temperature of the ink;
• step b) is carried out in an atmosphere having a relative humidity not exceeding 30%, or even 15%;
• during step b), the printing is carried out so that each end of the negative pattern of said at least one microstructure of the microstructured device to be manufactured is located at the edge of the substrate, so that each end can, on the device to be manufactured, forming an opening, such as a fluid inlet or outlet, so as to form a microstructure in the form of a channel;
• between step b) and step c), the following sub-steps are carried out: placing a microfluidic connection, partly at the level of the region of the pattern which is intended to form a channel opening and partly outside the substrate; and applying ink between said connection and the pattern;
• between steps b) and c), annealing is carried out, at a temperature advantageously between 10% and 80% of the melting temperature of the pattern;
• step c) is carried out by pouring the polymer onto the substrate printed by the pattern;
• the polymer introduced in step c) is chosen from: polydimethylsiloxane (PDMS), polyimides, agarose gels or an adhesive such as acrylic;
• the additive present in the polymer is chosen from a crosslinking agent, a photoinitiator or a solvent;
• said polymer intended to form the envelope has a melting temperature strictly greater than 110% of the sublimation or evaporation temperature of the ink forming the pattern;
• step e) is carried out by heating and by applying a pressure differential between the inside of the assembly formed at the end of step d) and the outside;
• the liquefaction then the evaporation of the ink in step e) is carried out by heating;
• the ink is chosen from:
  • linear glycols whose generic formula is C _2n H _4n+2 O ₂ where n is a positive integer greater than or equal to 1, preferably such that n=3, 4 or 5;
  • cyclohexanediol;
  • biphenyl;
  • tri(cyclohexyl)methane;
  • the alcohols of structural formula C _n H _2n + ₂ O where n is a positive integer greater than or equal to 1, preferably such that n=10, 11 or 12;
• during step b) several successive layers of ink are printed on top of each other;
• step b) is carried out by ink jet printing, using a printing nozzle and a liquid ink whose viscosity is less than or equal to 30 mPa.s ^-1 ;
• the distance between, on the one hand, said printing nozzle and, on the other hand, the substrate is between 0.5 mm and 20 mm; the size of an ink drop ejected from said printing nozzle is between 10µm and 100µm; the ink drop ejection frequency from said nozzle is between 50Hz and 5kHz; the substrate of a relative displacement of one relative to the other with a controlled relative displacement speed, between 1mm/s and 100mm/s;
• step b) is carried out using a syringe containing the ink;
• the distance between, on the one hand, one end of the syringe through which the ink is dispensed and, on the other hand, the substrate is between 0.1 mm and 1 mm; the ink flow dispensed by the end of said syringe is between 0.01 nl/s and 10 nl/s; the substrate on the one hand and, said end of the syringe on the other hand, being adapted to allow relative movement of one with respect to the other with a controlled relative speed of movement, between 0.1 mm/s and 10mm/s.

• la figure 1 représente un premier dispositif apte à mettre en oeuvre le procédé selon l'invention ;
• la figure 2 représente un deuxième dispositif également apte à mettre en oeuvre le procédé selon l'invention ;
• la figure 3 représente l'évolution de l'épaisseur d'un dispositif microfluidique (canal), obtenu par la mise en oeuvre du procédé selon l'invention, en fonction d'un paramètre de fabrication de ce dispositif ;
• la figure 4 représente un dispositif microfluidique obtenu avec le procédé selon l'invention.

The invention will be better understood and other aims, advantages and characteristics thereof will appear more clearly on reading the description which follows and which is given with regard to the appended drawings, in which:

• there figure 1 represents a first device capable of implementing the method according to the invention;
• there figure 2 represents a second device also able to implement the method according to the invention;
• there picture 3 represents the change in the thickness of a microfluidic device (channel), obtained by implementing the method according to the invention, as a function of a manufacturing parameter of this device;
• there figure 4 represents a microfluidic device obtained with the method according to the invention.

• a) fournir un substrat ;
• b) imprimer une encre, non solide, sur le substrat, l'encre se solidifiant au contact du substrat pour former un motif en négatif d'au moins une microstructure du dispositif microstructuré à fabriquer ;
• c) envelopper l'encre sous forme solide avec un polymère non réticulé et comportant un additif apte à permettre une réticulation dudit polymère, ledit polymère étant non miscible avec le motif obtenu à l'étape b) afin de former une enveloppe pour le motif, ledit polymère présentant une température de fusion strictement supérieure à la température de sublimation ou d'évaporation de l'encre formant le motif ;
• d) réticuler l'enveloppe ; puis
  polymère présentant une température de fusion strictement supérieure à la température de sublimation ou d'évaporation de l'encre formant le motif ;
• d) réticuler l'enveloppe ; puis
• e) sublimer ou, selon la nature de l'encre, liquéfier puis évaporer l'encre de sorte à former le dispositif microstructuré comportant ladite au moins une microstructure.

The invention relates to a method of manufacturing a microstructured device comprising the following steps:

• a) providing a substrate;
• b) printing a non-solid ink on the substrate, the ink solidifying on contact with the substrate to form a negative pattern of at least one microstructure of the microstructured device to be manufactured;
• c) enveloping the ink in solid form with a non-crosslinked polymer and comprising an additive capable of allowing crosslinking of said polymer, said polymer being immiscible with the pattern obtained in step b) in order to form an envelope for the pattern, said polymer having a melting temperature strictly higher than the sublimation or evaporation temperature of the ink forming the pattern;
• d) cross-linking the envelope; Then
  polymer having a melting temperature strictly higher than the sublimation or evaporation temperature of the ink forming the pattern;
• d) cross-linking the envelope; Then
• e) sublimating or, depending on the nature of the ink, liquefying then evaporating the ink so as to form the microstructured device comprising said at least one microstructure.

In the context of the invention, a microstructure is a structure of which at least two dimensions are less than 1000 microns.

This method can be implemented in different ways.

In particular, we have represented on the figure 1 a first device 100 capable of implementing step b).

On the figure 1 , a direct orthogonal coordinate system (O, X, Y, Z) has been represented.

The device 100 comprises a substrate 1 and a device 10 for printing by inkjet on the substrate 1.

The device 10 for printing by ink jet comprises a reservoir 11 in which ink is located, a heating means 12 for the ink located in the reservoir 11, a printing nozzle 13 and a heating means 14 for the ink located in the print nozzle 13.

The device 100 also comprises a first platen 20 mounted on the device 10 for inkjet printing. This first plate allows said device 10 to move along a predefined axis, in this case on the figure 1 , along the vertical axis OZ (vertical axis). It is thus possible to adjust as desired the distance, taken along the axis OZ, between the outlet S of the printing nozzle 13 and the substrate 1.

Device 100 also includes a second plate 30 on which substrate 1 is mounted. This second plate 30 allows the movement of the substrate 1 in the horizontal plane (O, X, Y). This horizontal plane is also the plane in which the substrate 1 extends. This makes it possible to give the desired shape to the ink (pattern deposited during step b) on the substrate 1. It should however be noted that the substrate 1 could be inclined, that is to say present an orientation comprising a component along the OZ (vertical) axis, and in particular with an inclination of up to 45° with respect to the OX axis.

Between the substrate 1 and the second plate 30, the device 100 can comprise a cooler, operating for example by the Peltier effect. This cooler 40 can be useful when the ink used, heated at the level of the jet printing device 10 of ink, needs to be cooled quickly. Finally, the device 100 can provide a means 50 for discharging the heat between the cooler 40 and the second plate 30.

Advantageously, the ink used by this ink jet printing technique has a viscosity of less than or equal to 30 mPa.s ⁻¹ .

We represented on the picture 2 a second device 100' also able to implement step b).

The implementation of the method according to the invention with the second device 100' is based on the use of a syringe 10' containing the ink, instead of the device 10 for printing by ink jet of the first device 100. Thus, the syringe 10' comprises a reservoir 11' in which the ink is located, a piston 15' to be able to eject the ink from said reservoir 11' and a heating means 12' to heat the ink present in tank 11'. It will be noted that the outlet of the syringe 10' is called S'.

Everything else is identical to what was described above for the first device 100 and in particular, it will be noted that the first plate 20 is then mounted on the syringe 10'.

With this second device 100′, it is thus possible to use inks whose viscosity is higher than with the first device 100. Indeed, with an inkjet printing technique (printing nozzle), one uses a liquid ink whose viscosity is generally less than or equal to 30 mPa.s ^-1 . If higher viscosities can be envisaged with an inkjet printing technique, the use of a syringe certainly makes it possible to remove such a constraint and to have access to inks, which although not solid, present a viscosity greater than 30 mPa.s ^-1 .

We will now describe various characteristics of the method according to the invention.

The substrate provided in step a) may be a hydrophobic material, chosen in particular from: polyimides (PI), silicones including polydimethylsiloxane (PDMS), polypropylene (PP), polytetrafluoroethylene (PTFE) or the copolymer of cyclic olefin (COC).

Alternatively, the substrate provided in step a) may be a hydrophilic material, chosen in particular from silicon, glass, cellulose, glass fibers.

• les glycols linéaires dont la formule brute générique est C_2nH_4n+2O₂ où n est un nombre entier positif supérieur ou égal à 1, de préférence tel que n = 3, 4 ou 5 ;
• le cyclohexanédiol ;
• le biphényl ;
• le tri(cyclohexyl)méthane ;
• les alcools de formule brute C_nH_2n+2O où n est un nombre entier positif supérieur ou égal à 1, de préférence tel que n = 10, 11 ou 12.

Furthermore, the ink may in particular be chosen from:

• linear glycols whose generic formula is C _2n H _4n+2 O ₂ where n is a positive integer greater than or equal to 1, preferably such that n=3, 4 or 5;
• cyclohexanediol;
• biphenyl;
• tri(cyclohexyl)methane;
• alcohols of structural formula C _n H _2n+2 O where n is a positive integer greater than or equal to 1, preferably such that n=10, 11 or 12.

In addition, the polymer intended to form the envelope may be chosen from polydimethylsiloxane (PDMS), polyimides, agarose gels or certain glues (acrylic, for example).

• substrat : polyimide
• encre (motif) :1,6-hexanediol (C₆H₁₄O₂), glycol linéaire avec n = 3 selon la formule brute générique rappelée précédemment
• polymère (enveloppe) : polydiméthylsiloxane (PDMS)

In particular, the following association can be provided (example 1 detailed below):

• substrate: polyimide
• ink (pattern): 1,6-hexanediol (C ₆ H ₁₄ O ₂ ), linear glycol with n = 3 according to the generic formula given above
• polymer (shell): polydimethylsiloxane (PDMS)

• substrat : verre
• encre (motif) :1,6-hexanediol
• polymère (enveloppe) : polydiméthylsiloxane (PDMS)

We can also provide the following association (example 2 detailed below):

• substrate: glass
• ink (pattern): 1,6-hexanediol
• polymer (shell): polydimethylsiloxane (PDMS)

It will be noted that the two examples provided above, and detailed subsequently, make it possible to produce a microstructure in the form of a cavity. Indeed, the 1,6-hexanediol ink can pass through the PDMS envelope when this ink is sublimated or evaporated.

• substrat : polyimide
• encre (motif) : 1,6-hexanediol
• polymère (enveloppe) : acrylique

Also in particular, the following association may be provided:

• substrate: polyimide
• ink (pattern): 1,6-hexanediol
• polymer (shell): acrylic

• substrat : gel d'agarose
• encre (motif) : biphényl
• polymère (enveloppe) : gel d'agarose

Yet another possibility is to provide the following association:

• substrate: agarose gel
• ink (pattern): biphenyl
• polymer (shell): agarose gel

These are only examples and other combinations are possible.

Between step a) and step b), the substrate can be treated to improve its adhesion strength with the ink to be deposited and/or the polymer intended to form the envelope. The advantage of such a treatment depends mainly on the nature (type of material used) of the substrate. This treatment can be chosen from among a plasma treatment, in particular at reduced pressure and under a flow of oxygen, a treatment by ultraviolet-ozone or a treatment by chemical oxidation.

• La distance entre d'une part, ladite buse d'impression et d'autre part, le substrat est comprise entre 0,5mm et 20mm ;
• La taille d'une goutte d'encre éjectée par ladite buse d'impression est comprise entre 10µm et 100µm ;
• La fréquence d'éjection des gouttes d'encre de ladite buse est comprise entre 50Hz et 5kHz ;
• Le substrat d'une part et ladite buse d'impression d'autre part, étant adaptés pour autoriser un déplacement relatif de l'un par rapport à l'autre avec une vitesse de déplacement relative contrôlée, comprise entre 1mm/s et 100mm/s.

From a practical point of view, the method according to the invention is such that, during step b) and in the case of inkjet printing:

• The distance between, on the one hand, said printing nozzle and, on the other hand, the substrate is between 0.5 mm and 20 mm;
• The size of a drop of ink ejected by said printing nozzle is between 10 μm and 100 μm;
• The ink drop ejection frequency from said nozzle is between 50Hz and 5kHz;
• The substrate on the one hand and said printing nozzle on the other hand, being adapted to allow relative movement of one relative to the other with a controlled relative speed of movement, between 1mm/s and 100mm/ s.

The four parameters mentioned above (drop size, nozzle end distance from the substrate, drop ejection frequency and relative displacement speed between nozzle and substrate) contribute to the definition of the geometry of the pattern deposited on the substrate.

Thus, if the distance between, on the one hand, said printing nozzle through which the ink is ejected and, on the other hand, the substrate is too small, resolution is lost. If this same distance is too great, the drop of ink risks being disturbed in its descent towards the substrate. It is therefore more advantageous to work in the distance range mentioned above.

The frequency of ejection of the drops and the relative displacement speed mentioned above make it possible to manage the distance separating two drops successively deposited on the substrate. From a very practical point of view, the drops should not be too far apart if one wants to obtain a microstructure of controlled size (this is particularly the case for an application microfluidics for which we seek to define a channel). Conversely, the drops should also not be too close to correctly manage the thickness of the pattern.

The size of a drop makes it possible to manage the quantity of ink deposited locally on the substrate, which has in particular an influence on the width and the thickness of the pattern.

• La distance entre d'une part, une extrémité de la seringue par laquelle l'encre est dispensée et d'autre part, le substrat est comprise entre 0,1mm et 1mm ;
• Le débit d'encre dispensé par l'extrémité de ladite seringue est compris entre 0,01 nl/s (nanolitre par seconde) et 10 nl/s ;
• Le substrat d'une part et, ladite extrémité de seringue d'autre part, étant adaptés pour autoriser un déplacement relatif de l'un par rapport à l'autre avec une vitesse de déplacement relative contrôlée, comprise entre 0,1mm/s et 10mm/s.

Also from a practical point of view, the method according to the invention is such that, during step b) and in the case of printing with a syringe:

• The distance between, on the one hand, one end of the syringe through which the ink is dispensed and, on the other hand, the substrate is between 0.1 mm and 1 mm;
• The ink flow dispensed by the end of said syringe is between 0.01 nl/s (nanolitre per second) and 10 nl/s;
• The substrate on the one hand and said end of the syringe on the other hand, being adapted to allow relative movement of one with respect to the other with a controlled relative speed of movement, between 0.1 mm/s and 10mm/s.

The three parameters mentioned above (dispensed volume, syringe end distance from the substrate and relative displacement speed between the syringe and the substrate) contribute to the definition of the geometry of the pattern deposited on the substrate.

Thus, if the distance between, on the one hand, the end of the syringe through which the ink is dispensed and, on the other hand, the substrate is too small, resolution is lost. If this same distance is too great, the column of liquid destabilizes. It would be perfectly possible not to operate in the aforementioned range, but this choice is more advantageous because it facilitates implementation.

The flow rate of ink dispensed and the relative displacement speed mentioned above make it possible to manage the quantity of ink deposited locally on the substrate, which has in particular an influence on the width and the thickness of the pattern.

Furthermore, at least during step b), the substrate can be cooled to a temperature below the solidification temperature of the ink. For certain inks whose printing temperature (non-solid) is relatively high compared to the solidification temperature, this makes it possible to accelerate the solidification of the ink on the substrate. This makes it possible, for certain inks, to improve the control of the geometry of the pattern deposited in step b). Indeed, if the ejection or deposition conditions often allow complete control of the geometry of the pattern deposited on the substrate, it turns out that, for certain inks, this cooling avoids excessive spreading of the drop on the substrate. before its solidification. This makes it possible to retain the geometry of the desired pattern with the ejection or deposition conditions mentioned previously. Another consequence is that this makes it possible to accelerate the manufacture of the microstructured device.

It will be noted that the cooling of the substrate can be managed by a Peltier effect cell.

Step b) can be carried out under vacuum (high vacuum) or under a neutral atmosphere, for example under air. When this step is carried out in a neutral atmosphere, in particular in air, it is possible in particular to envisage operating at atmospheric pressure. Working under air at atmospheric pressure facilitates implementation. Typically, it is possible to envisage implementing step b) in a pressure range of between 10 ⁻⁴ Pa and 1.013×10 ⁵ Pa.

When one is not under vacuum, different types of atmosphere can be envisaged, in particular in ambient air. In the latter case, it may be advantageous, especially when a hydrophilic ink is used, to ensure that the relative humidity does not exceed, at least during this step b), 30%, or even 15 %. This prevents the ink, in its path between the nozzle or, as the case may be, the end of the syringe on the one hand and the substrate on the other hand, from absorbing moisture; which can have an impact on the resolution of the deposition of the pattern on the substrate. This also makes it possible to avoid the possible condensation of water on the substrate (whether the latter is hydrophilic or hydrophobic), which is then also favored by the cooling of the substrate, with the possible harmful consequence of poor control of the shape and pattern resolution.

Step c) can be carried out by pouring the polymer onto the substrate printed by the pattern. The polymer, intended to form the envelope, is then deposited in liquid form. Furthermore, it should be noted that the polymer chosen to form the envelope is immiscible with the ink (pattern). Otherwise, it would not be possible to obtain the microstructured device, namely to simply define a cavity or a channel.

It should be noted that the polymer comprises an additive capable of allowing the crosslinking of the polymer intended to form the envelope, during the subsequent stage d). From a practical point of view, the polymer/additive mixture is prepared upstream so that a polymer containing this additive is poured (poured).

Step d) (crosslinking of the envelope) is therefore based on the presence of this additive.

This additive can be a cross-linking agent such as methylhydrosiloxane, a photo-initiator such as 1-Hydroxy-cyclohexyl-phenyl-ketone or a solvent such as formaldehyde.

In the case where the additive is a crosslinking agent, and depending on the nature of this crosslinking agent and/or of the polymer, the crosslinking can be carried out at ambient temperature, possibly aided by low heating to accelerate the crosslinking. Still when the additive is a crosslinking agent, and if the nature of the crosslinking agent and/or that of the polymer does not allow crosslinking at ambient temperature, the crosslinking can be carried out by heating.

In the case where the additive is a photoinitiator, the crosslinking can be carried out by subjecting the polymer to ultraviolet radiation. A photo-initiator can in particular be envisaged with certain adhesives, which then become crosslinkable by ultraviolet rays.

Finally, in the case where the additive is a solvent, the crosslinking takes place by simple evaporation of the solvent, which generally takes place at room temperature. Once the solvent has evaporated, the polymer crosslinks.

In step d), the negative pattern (ink) is in solid form.

Thus, when the additive present in the non-crosslinked polymer is a crosslinking agent, and it is necessary to heat the polymer to ensure its crosslinking, the crosslinking temperature of the polymer should be lower than the melting temperature of the polymer. ink, even if the crosslinking can provide, in order to finalize the crosslinking, a brief passage at a temperature higher than the melting temperature of the pattern. In the latter case, a small part of the pattern may liquefy, but since the polymer is for the most part already crosslinked, this then does not involve any modification of the interface between the pattern and the envelope. In particular, in many cases, it is possible to envisage crosslinking at room temperature, for 24 hours, followed by finalization of the crosslinking at higher temperature, in particular above the melting point of the pattern, without however spend this pattern in the gaseous state, for a few tens of minutes, or even an hour.

Advantageously, provision may be made for the polymer forming the envelope to have a crosslinking temperature less than or equal to 90% of the melting point of the ink (pattern).

Depending on the ink used, you can either sublimate the pattern or liquefy it and then evaporate it.

Thus, to sublimate the pattern, step e) is carried out by heating and by applying a pressure differential between the inside of the assembly formed at the end of step d) and the outside. This makes it possible to place oneself, in the phase diagram of the ink (pattern), on a pressure/temperature couple which directly allows the transition from the solid state to the vapor state. When this is possible, it is particularly advantageous because the level of heating of the assembly formed in step d), and therefore the energy expended, is limited to put the pattern in the form of vapor and therefore eliminate it in order to form the microstructure (cavity, channel, etc.).

As a variant, or failing that, when it is not reasonably possible to provide sublimation of the ink (pattern), step e) is carried out by heating in order to ensure the liquefaction, then the vaporization of the ink (pattern).

In both cases, putting the ink (pattern) in vapor form is particularly advantageous insofar as the extraction of the vapors is very easy.

We also understand why it is important to choose a polymer for the envelope with certain physical properties. Indeed, during the heating aimed at causing the ink (pattern) to disappear in order to define said at least one microstructure, the envelope must remain in solid form. And it is therefore for this reason that the polymer chosen for the envelope must have a melting temperature (transition from the solid state to the liquid state) strictly higher than the sublimation temperature of the ink (pattern), or as the case may be, higher than the evaporation temperature of the ink (pattern).

This ensures that the envelope remains in place during the implementation of step e).

Advantageously, provision may be made for the polymer forming the envelope to have a melting temperature strictly greater than or equal to 110% of the sublimation temperature or, as the case may be, of the evaporation temperature of the ink forming the pattern. This amounts to saying that the ink forming the pattern has a sublimation temperature or, depending on the case, an evaporation temperature, substantially less than or equal to 90% of the melting temperature of the envelope.

It may be advantageous to carry out, between steps b) and c), an annealing. Such annealing makes it possible to reduce the roughness of the pattern deposited in step b). Indeed, once the pattern has solidified and despite the care given to the deposition conditions, it can be seen that the pattern, in solid form, has a non-negligible roughness. Consequently, this roughness may be found on the microstructure to be formed (negative). In particular, for microfluidic applications, the roughness can change the flow conditions in the microstructure (channel) and consequently the pressure drops and/or the heat exchanges. For other applications, for example in optics, it is understood that this roughness within the microstructure (cavity) can also modify the analysis conditions.

It is understood that such annealing, like any annealing, will be carried out at a temperature strictly below the melting temperature of the pattern (ink) deposited in step b) on the substrate and typically in a range of values between 10 % and 80% of the melting temperature of the pattern (ink, in solid form).

With the method according to the invention, it is possible to produce a device comprising a closed (cavity) or open (channel) microstructure between the substrate and the envelope.

A cavity may be of interest for certain applications, for example in optics or acoustics.

However, in the context of the invention, the method will be more particularly for manufacturing a microfluidic device, in which the microstructure is a channel (therefore comprising openings, such as an inlet and an outlet for a fluid).

In the case where the microstructure is a channel, the printing carried out during step b), is carried out so that each end of the negative pattern of said at least one channel of the microfluidic device to be manufactured is located at the edge of the substrate, so that each end can, on the device to be manufactured, form a channel opening, such as a fluid inlet or outlet.

In order to facilitate the connection of the microfluidic device manufactured with the method according to the invention to any external system, provision may also be made to place a microfluidic connection, partly at the level of the region of the pattern which is intended to form a channel opening. and partly outside the substrate; then applying ink between said connection and the pattern.

The connection thus formed, which forms an integral part of the fabricated microfluidic device, then protrudes partly from the substrate (and therefore from the envelope). This therefore greatly facilitates the fluidic connection to an external system.

We will now describe a few embodiments of a microfluidic device with a method in accordance with the invention.

Example 1

Substrate: a polyimide substrate was supplied (step a)), in this case a ^Kapton® HN offered by the company DuPont de Nemours.

In the present case, the ^Kapton® HN used is stable at the temperatures used in this example.

Pattern (ink): 1,6-hexanediol (C ₆ H ₁₄ O ₂ ) was chosen as the ink.

This ink has the following properties: T _fusion = 45°C (air, atmospheric pressure) and T _vaporization = 250°C (air, atmospheric pressure).

To implement step b), this ink was heated to 65°C (therefore, in liquid form) to carry out the printing on the substrate, according to the inkjet printing technique (this temperature allows in particular to ensure that the dynamic viscosity of the liquid ink is less than 30 mPa.s).

The print nozzle was positioned 5mm from the substrate.

Each drop of ink ejected from the print nozzle had a diameter of 60µm. The drops were ejected from the print nozzle at a frequency of 100Hz.

The relative speed between the printing nozzle and the substrate was 4mm/s.

The printing was carried out so that each end of the negative pattern of the microstructure to be manufactured is located at the edge of the substrate, so that each end can, on the device to be manufactured, form a channel opening (an entrance and a fluid outlet).

Furthermore, during printing, the substrate was cooled to -10°C (with a Peltier effect cell) to ensure faster solidification of the ink.

Envelope (polymer):
The polymer used is polydimethylsiloxane (PDMS), in this case Sylgard ^® 184.

This polymer was mixed with a crosslinking agent, in this case methylhydrosiloxane, in a mass ratio of 1/10 (1 for the crosslinking agent and 10 for the polymer).

The polymer thus prepared was cast, at room temperature, on the substrate printed with the pattern, to implement step c).

Then, crosslinking step d) was implemented: crosslinking for 24 hours at room temperature.

Once cured, the PDMS mentioned above is stable over the temperature range of -45°C to 200°C.

Step e) was then carried out.

To this end, the assembly obtained at the end of step d) was heated to a temperature of 100° C. and under a pressure of 0.1 bar.

Under these conditions, the motif was sublimated.

Example 2

In this second example, the ^Kapton® substrate (Example 1) is replaced by a glass substrate.

The printing step was carried out under air, with a relative humidity of less than 15%. In fact, the glass has a hydrophilic nature whereas the ^Kapton® used as substrate in Example 1 has a hydrophobic nature.

Everything else is the same as the first example.

End of example 2.

Finally, it should be noted that at the end of the manufacturing process, a device is obtained comprising an envelope on a substrate. As indicated above, depending on the nature (material) of the envelope and/or the nature (material) of the substrate (material), it may happen that the cohesion between the envelope and the substrate is relatively weak. . If it is desired to ensure that the polymer holds on the substrate, the step of treatment (plasma, etc.) of the substrate mentioned above can be provided.

However, it is also possible to take advantage of this lack of cohesion between the substrate and the envelope to recover only the envelope. This envelope can then serve as a mold for other uses.

Example 3

In this third example, the substrate is made of glass.

The printing step was carried out under air, with a relative humidity of less than 15%.

The rest is identical to example 1, except for the fact that the printing step (step b)) for which several successive layers of ink are printed on top of each other.

From a practical point of view, this is done by making one or more additional passes of the printing nozzle, above the first layer of ink deposited in the first pass, the conditions of deposition of the or each pass additional being identical to the conditions of deposit of the first passage.

There picture 3 represents the change in the height of the channel thus obtained as a function of the number of layers of ink successively deposited during step b). Note that this relationship is linear. This is linked to the fact that the ink deposition conditions are identical from one layer to another.

In the end, this therefore makes it possible to define a channel whose section has a high aspect ratio (= height/width ratio).

Example 4

In this fourth example, the substrate is made of glass.

The printing step was carried out under air, with a relative humidity of less than 15%.

The rest is identical to example 1, except that the printing step (step b)) is carried out in a specific way in order to be able to manufacture intersecting channels.

Thus, after having deposited ink, in accordance with example 1, in order to form a first channel part PPC and deposited ink to form other channel parts APC1, APC2 on either side of the first channel part, these other channel parts being intended to cross the first channel part, an arch should be made to connect the channel parts APC1, APC2 by passing over the first channel part PPC.

• Les gouttes d'encre ont été éjectées à une fréquence de 4Hz ;
• La vitesse relative entre la buse d'impression et le substrat était de 0,12 mm/s.

To this end, certain deposition conditions of step b) of printing have been modified. As it happens :

• The ink drops were ejected at a frequency of 4Hz;
• The relative speed between the printing nozzle and the substrate was 0.12 mm/s.

There figure 4 shows the arch A thus formed, forming an integral part of the channel.

Claims (20)

1. A method for manufacturing a microstructured device comprising the following steps:

   a) providing a substrate

   b) printing a non-solid ink on the substrate, the ink solidifying upon contact with the substrate to form a negative pattern of at least one microstructure of the microstructured device to be fabricated;

   c) covering the ink in solid form with a non-crosslinked polymer comprising an additive capable of allowing crosslinking of said polymer, said polymer being immiscible with the pattern obtained in step b) in order to form a cover for the pattern, said polymer having a melting temperature strictly higher than the sublimation or evaporation temperature of the ink forming the pattern;

   d) cross-linking the cover; then

   e) sublimating or, depending on the nature of the ink, liquefying and then evaporating the ink so as to form the microstructured device comprising said at least one microstructure.
2. The method according to claim 1, wherein the substrate provided in step a) is a hydrophobic material selected from: polyimides (P!), silicones including polydimethylsiloxane (PDMS), polypropylene (PP), polytetrafluoroethylene (PTFE), cyclic olefin copolymer (COC), or a hydrophilic material selected from silicon, glass, cellulose, glass fibres.
3. The method according to one of the preceding claims, wherein between step a) and step b), a treatment of the substrate is performed to improve its adhesion strength with the ink to be deposited and/or the polymer intended to form the cover.
4. The method according to one of the preceding claims, wherein, at least during step b), the substrate is cooled to a temperature below the solidification temperature of the ink.
5. The method according to one of the preceding claims, wherein step b) is carried out in an atmosphere having a relative humidity not exceeding 30% or even 15%.
6. The method according to one of the preceding claims, wherein in step b), the printing is carried out so that each end of the negative pattern of said at least one microstructure of the microstructured device to be manufactured is located at the edge of the substrate, so that each end can, on the device to be manufactured, form an opening, such as a fluid inlet or outlet, so as to form a microstructure in the form of a channel.
7. The method according to the preceding claim, wherein, between the step b) and step c), the following sub-steps are performed:

   - placing a microfluidic connection, partly at the region of the pattern which is intended to form a channel opening and partly outside the substrate; and

   - applying the ink between said connection and the pattern.
8. The method according to one of the preceding claims, wherein, between the steps b) and c), annealing is performed, at a temperature advantageously between 10% and 80% of the melting temperature of the pattern.
9. The method according to one of the preceding claims, in which the step c) is carried out by casting the polymer onto the substrate printed by the pattern.
10. The method according to one of the preceding claims, wherein the polymer introduced in step c) is selected from: polydimethylsiloxane (PDMS), polyimides, agarose gels or an adhesive such as acrylic.
11. The method according to one of the preceding claims, wherein the additive present in the polymer is selected from a cross-linking agent, a photoinitiator or a solvent.
12. The method according to one of the preceding claims, wherein said polymer for forming the cover has a melting temperature strictly 110% of the sublimation or evaporation temperature of the ink forming the pattern.
13. The method according to one of the preceding claims, wherein the sublimation of step e) is carried out by heating and by applying a pressure differential between the inside of the assembly formed after step d) and the outside.
14. The method according to one of claims 1 to 16 wherein the liquefaction and subsequent evaporation of the ink in step e) is carried out by heating.
15. The method according to one of the preceding claims, wherein the ink is selected from:

    - linear glycols with the generic empirical formula C_2nH_4n+₂O₂ where n is a positive integer greater than or equal to 1, preferably such that n = 3, 4 or 5;

    - cyclohexanediol;

    - biphenyl;

    - tri(cyclohexyl)methane;

    - alcohols with the gross formula C_nH_2n+₂O where n is a positive integer greater than or equal to 1, preferably such that n = 10, 11 or 12.
16. The method according to one of the preceding claims, wherein in the step b) a plurality of successive layers of ink are printed on top of each other.
17. The method according to one of the preceding claims, wherein the step b) is carried out by ink jet printing, using a printing nozzle and a liquid ink whose viscosity is less than or equal to 30 mPa.s^-1.
18. The method according to the preceding claim, wherein:

    - the distance between, on the one hand, said printing nozzle and, on the other hand, the substrate is between 0.5 mm and 20 mm;

    - the size of an ink drop ejected by said printing nozzle is between 10µm and 100µm;

    - the frequency of ejecting ink drops from said nozzle is between 50Hz and 5kHz;

    - the substrate on the one hand and said printing nozzle on the other hand being adapted to allow relative movement of one with respect to the other with a controlled relative movement speed of between 1mm/s and 100mm/s.
19. The method according to one of claims 1 to 16, wherein the step b) is performed by means of a syringe containing the ink.
20. The method according to the preceding claim, wherein:

    - the distance between, on the one hand, an end of the syringe through which the ink is dispensed and, on the other hand, the substrate is between 0.1mm and 1mm;

    - the flow rate of ink dispensed by the end of said syringe is between 0.01 nl/s and 10 nl/s;

    - the substrate, on the one hand, and said syringe tip, on the other hand, being adapted to allow relative displacement of one with respect to the other with a controlled relative displacement speed of between 0.1mm/s and 10mm/s.

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